Clinical Trial: Efficacy, Safety and Tolerability of ISIS 304801 in People With Partial Lipodystrophy With an Open-Label Extension
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Randomized, Double Blind, Placebo-Controlled Study to Assess Efficacy, Safety and Tolerability of ISIS 304801 in Patients With Partial Lipodystrophy With an Open-Label E
Brief Summary:
Background:
Partial lipodystrophy is a deficiency of body fat in parts of the body (usually the arms and legs). People with partial lipodystrophy often get high blood triglyceride (fat) level, insulin resistance, diabetes and other problems. Researchers think the new drug ISIS 304801 can help treat health problems caused by partial lipodystrophy.
Objective:
To see if ISIS 304801 will improve blood fat (triglyceride levels), diabetes, and liver disease, and reduce some risks for heart disease caused by partial lipodystrophy.
Eligibility:
Adults at least 18 years old with partial lipodystrophy.
Design:
Participants will be screened during a 1-week stay at NIH. They will have:
Blood and urine tests
Physical exam.
Assignment to get either the study drug or placebo.
Instructions for how to inject the drug.
Body measurements.
Heart tests.
Participants will give themselves injections of the drug or placebo once a week at home. Some may test blood sugar by finger pricks. They will have monthly phone calls and nurse visits to take blood tests.
After 4 months, participants may continue the study for 1 year. All participants will get the study drug.
Background:
Lipodystrophy is a rare disease of deficient adipose mass, characterized by severe hypertriglyceridemia as well as insulin resistance, diabetes mellitus, fatty liver disease, acute pancreatitis, and early cardiovascular events. Apolipoprotein C-III (apoC-III) regulates triglyceride metabolism, and apoC-III levels strongly correlate with serum triglycerides in a variety of patient populations. Patients with genetically low levels of apoC-III have lower triglycerides and reduced cardiovascular disease, while individuals with genetically elevated levels of apoC-III have higher triglycerides and increased non-alcoholic fatty liver disease and insulin resistance. Pharmacologic reduction of apoC-III using anti-sense oligonucleotides (ASOs) reduce triglycerides by ~60-70% in a tested patient populations.
Aim:
The purpose of this study is to determine if apoC-III reduction using an ASO to apoC-III (ISIS 304801) will reduce triglycerides and improve insulin resistance, diabetes, and hepatic steatosis in patients with lipodystrophy.
The primary hypothesis to be tested is:
-
ISIS 304801will reduce log10 fasting serum triglycerides.
Secondary and tertiary hypotheses to be tested are:
- ISIS 304801will improve glucose metabolism by improving insulin resistance.
- ISIS 304801 will reduce hepatic steatosis.
- ISIS 304801 will improve cardiovascular risk markers.
We will also explore the mechanism
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Current Primary Outcome: To evaluate the efficacy of 16 weeks of ISIS 304801compared to placebo on the change inlog10 fasting triglycerides (TG). [ Time Frame: 16 weeks ]
Original Primary Outcome: To evaluate the efficacy of 4 months of ISIS 304801 as compared to immediately prior to treatment (pre-post within subject comparison) on the percent change in fasting triglycerides (TG). [ Time Frame: 4 months ]
Current Secondary Outcome: To evaluate the efficacy of 16 weeks of ISIS 304801 as compared to placebo (between group comparison) on additional lipid, glycemic, hepatic, and cardiovascular parameters, as well as safety and tolerability of ISIS 304801. [ Time Frame: 16 weeks ]
Original Secondary Outcome: Secondary Outcome Measure: To evaluate the efficacy of 4 months of ISIS 304801 as compared to immediately prior to treatment (pre-post within subject comparison) on additional lipid, glycemic, hepatic, and cardiovascular parameters, as well as... [ Time Frame: 4 months ]
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: December 23, 2015
Date Started: December 17, 2015
Date Completion: December 31, 2018
Last Updated: April 20, 2017
Last Verified: January 13, 2017
